ADENOSINE-DEAMINASE DEFICIENCY IN ADULTS

Adenosine deaminase (ADA) deficiency typically causes severe combined immunodeficiency (SCID) in infants. We report metabolic, immunologic, and genetic findings in two ADA-deficient adults with distinct phenoty pes. Patient no. 1 (39 years of age) had combined immunodeficiency. Sh e had frequent infections, lymphopenia, and recurrent hepatitis as a c hild but did relatively well in her second and third decades. Then she developed chronic sinopulmonary infections, including tuberculosis, a nd hepatobiliary disease; she died of viral leukoencephalopathy at 40 years of age. Patient no. 2, a healthy 28-year-old man with normal imm une function, was identified after his niece died of SCID. Both patien ts lacked erythrocyte ADA activity but had only modestly elevated deox yadenosine nucleotides. Both were heteroallelic for missense mutations : patient no. 1, G216R and P126Q (novel); patient no. 2, R101Q and A21 5T. Three of these mutations eliminated ADA activity, but A215T reduce d activity by only 85%. Owing to a single nucleotide change in the mid dle of exon 7, A215T also appeared to induce exon 7 skipping. ADA defi ciency is treatable and should be considered in older patients with un explained lymphopenia and immune deficiency, who may also manifest aut oimmunity or unexplained hepatobiliary disease. Metabolic status and g enotype may help in assessing prognosis of more mildly affected patien ts. (C) 1997 by The American Society of Hematology.